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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 253 records · Page 14Linked to original sources

Synthesis and biological activity of N6-(n-alkylureido)purine ribonucleosides and their 5'-phosphates.

Syntheses and biological activities of 12 N6-(n-alkylureido)purine ribonucleosides (alkyl chain length of 1--10, 16, and 18 carbons) and three N6-(n-alkylureido)purine ribonucleoside 5'-phosphates (chain length of 4, 9, and 10 carbons) are described. The N6-(n-alkylureido)purine ribonucleosides were prepared by a reaction of (2',3',5'-tri-O-acetyl-beta-D-ribofuranosyl)-9H-purine-6-carbamate and n-alkylamine in refluxing pyridine. The 5'-nucleotides were prepared by direct phosphorylation of the corresponding ribonucleoside with phosphorus oxychloride and triethyl phosphate. Some N6-(n-alkylureido)purine ribonucleosides (n-octyl, n-nonyl, and n-decyl) and their nucleotides showed a marked antiproliferative activity against L-1210 cells in culture.

Animals↗

Adenosine deaminase activity in patients with carcinoma of the bladder.

Adenosine deaminase is an important enzyme in purine metabolism, and patients with abnormal lymphocyte and erythrocyte adenosine deaminase levels have been shown to have impaired immune competence. Since immune factors have been shown to be important in patients with transitional cell carcinoma of the bladder we studied adenosine deaminase activity in the hemic cells of 48 patients with this tumor. Lymphocyte adenosine deaminase levels were elevated in patients with transitional cell carcinoma and correlated with stage, activity, clinical course and tumor resection but not with tumor grade. Erythrocyte adenosine deaminase levels also were elevated in patients with transitional cell carcinoma but did not correlate with other disease parameters. Lymphocyte adenosine deaminase activity in patients with transitional cell carcinoma may be a sensitive indicator of disease activity and further studies may provide insight into the host-tumor relationship at the enzyme level.

Adenosine Deaminase↗

Prednimustine therapy for advanced prostatic cancer.

23 patients with advanced, hormonal-resistant, prostatic cancer were treated with daily oral prednimustine--a combination of prednisolone and chlorambucil. 8 patients (35%) subjectively responded with disappearance of skeletal pain and improvement in appetite, weight and sense of well being. 3 patients had objective evidence of tumour regression. Clinical toxicity was moderate, and only occasional myelosuppression was encountered. The ease of administration and predictable toxicity of prenimustine make it a potentially useful agent, alone or in combination, for advanced prostatic cancer.

Adrenal Glands↗

Diet in the epidemiology of cancer of the colon and rectum.

We examined the diets as reported in interviews of 256 white male patients with cancer of the colon and of 330 white male patients with cancer of the rectum. Controls were 783 patients with nonneoplastic, nondigestive system diseases distributed by age similarly to the colon cancer patients and 628 patients with nonneoplastic, nondigestive diseases distributed by age like those with cancer of the rectum. We found no increase in risk for cancer of the colon or rectum regardless of the amounts of beef or other meats ingested. However, we found an increase in risk of colon cancer with decreases in the frequency with which vegetables were eaten. A study of 214 females with cancer of the colon and 182 females with cancer of the rectum yielded similar results. The decrease in risk we found associated with frequent ingestion of vegetables, and especially cabbage, Brussels sprouts, and broccoli, is consistent with the decreased numbers of tumors observed in animals challenged with carcinogens and fed compounds found in these same vegetables.

Animals↗

Studies of lymphocyte adenosine deaminase activity in patients with renal and transitional cell carcinoma.

Adenosine deaminase (ADA) is a critical enzyme in purine metabolism and lymphocyte ADA activity is specifically related to immunocompetence in man. Since immunologic factors are relevant in patients with renal and transitional cell carcinoma, we studied lymphocyte ADA activity in these patients. In renal adenocarcinoma patients lymphocyte ADA activity was reduced. Such reductions were most marked in low-as compared to high-stage lesions. Nephrectomy resulted in a rise and disease progression in a decline in ADA activity. In contrast, bladder, carcinoma patients showed elevated lymphocyte ADA activity most marked in high-stage lesions. Disease progression was associated with a rise and tumor resection with a decline in lymphocyte ADA activity. Discordance in patterns of lymphocyte ADA activity when patients with renal and transitional cell carcinoma are compared suggests unique host-tumor interactions at the enzyme level. Studies of ADA may offer insight into molecular aspects of immune mechanisms.

Adenocarcinoma↗

Phase II study of melphalan in colorectal carcinoma.

In a prospective phase II study, 25 patients with advanced (Duke's D) colorectal adenocarcinoma received 0.25 mg/kg of melphalan orally daily for 4 days every 28 days. There were 17 men and eight women. All patients had measurable areas of known malignant disease which served as objective indicators of the response to chemotherapy. All patients were evaluated for at least two cycles of therapy. Each patient had had previous treatment with 5-fluorouracil and, in addition, 24 of 25 patients had had treatment with methyl-CCNU; all patients had disease progression with both regimens. Toxicity consisted of mild gastrointestinal symptoms and transient leukopenia (wbc count less than 4000/mm3) in nine of 25 (36%) patients and thrombocytopenia (platelet count less than 100,000/mm3) in six of 25 (24%). One of 25 (4%) patients had an objective response for 12 weeks, 15 of 25 (60%) had disease progression, and nine of 25 (36%) remained stable for 2 months. We conclude that melphalan is ineffective for patients with metastatic colorectal carcinoma who have previously failed to respond to both 5-fluorouracil and methyl-CCNU.

Adenocarcinoma↗

Adenosine deaminase activity in patients with renal adenocarcinoma.

Erythrocyte and lymphocyte adenosine deaminase (ADA) levels were studied in 31 patients with renal cell carcinoma (RCC). Decreased lymphocyte ADA levels occurred in patients with RCC. Erythrocyte ADA levels were reduced only in blood type B and O patients. Nephrectomy resulted in a rise in lymphocyte and erythrocyte ADA levels. Progression of clinical disease was associated with a fall in lymphocyte ADA values in all patients and with a rise in erythrocyte levels only in blood type A patients. Our results suggest that changes in erythrocyte and lymphocyte ADA levels in RCC patients are acquired and may offer insight into host-tumor interactions.

ABO Blood-Group System↗

Nephrotic syndrome associated with gastric cancer.

A patient whose nephrotic syndrome was controlled by steroids and cyclophosphamide was found to have gastric cancer. After removal of the tumor and discontinuing the steroid therapy, no recurrence of the clinical signs of nephrotic syndrome appeared, but moderate proteinuria persisted. The literature regarding the association of nephrotic syndrome with malignancies is reviewed.

Adenocarcinoma↗

Combined therapy of advanced prostatic carcinoma with estramustine and prednimustine.

We treated 21 patients with stage D prostatic adenocarcinoma who had had unsuccessful hormonal therapy with a combination of 600 mg. per M.2 per day estramustine phosphate (Estracyt) and 15 mg. per M.2 per day prednimustine (Stereocyt, Leo 1031) in daily oral doses. Estramustine is a combination of estradiol and nitrogen mustard, and alone has shown objective responses in advanced prostatic cancer. Prednimustine is an ester of chlorambucil and prednisone. The preliminary results (after 2 to 9 months of therapy) show 5 patients (24 per cent) did not benefit from the drug and 7 patients (33 per cent) are stable. These preliminary results indicate the possible advantage of adding an alkylating agent (prednimustine) to estramustine in advanced prostatic carcinoma. Currently, a national randomized trial by the National Prostatic Cancer Project is evaluating this therapeutic innovation.

Aged↗

CEA monitoring of palliative treatment for colorectal carcinoma.

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable.

Adult↗

Canine and human renal toxicity of inosine dialdehyde (NSC 118994).

A new antitumor agent, inosine dialdehyde, has shown minimal hematologic, but dose limiting, renal toxicity. The renal impairment is tubular necrosis due to reduction in renal blood by the drug. In addition, elevated serum calcium will return to normal within one week of drug administration. This effect is not secondary to urinary calcium excretion, but possibly an alteration of bone metabolism.

Acute Kidney Injury↗

Preliminary clinical study of prednimustine in lung cancer.

Prednimustine is a prednisolone ester of chlorambucil which has been found effective in a variety of tumors. Eleven patients with advanced carcinoma of the lung (5 adenocarcinoma, 3 squamous cell carcinoma, 2 small cell carcinoma and 1 large cell carcinoma) were treated at a dosage of 40 mg. per day. Nine had previously failed on combination chemotherapy. No objective responses were observed. Leukopenia or thrombocytopenia were found in 4 patients with nadirs of 2,000 WBC and 60,000 platelets. The lack of response may be a function of the inability of lung carcinoma to concentrate the drug as shown with radioactive labeled Prednimustine. The malignant cells may lose their glucocorticoid binding capacity normally present in the lung. Determination of glucocorticoid binding capacity or Prednimustine uptake might predict the effectiveness of Prednimustine in the treatment of tumor. Prednimustine was well tolerated and may be given safely in advanced malignancies. Further studies with high intermittent doses and selection of tumors with steroid binding properties are now in progress.

Adenocarcinoma↗

Synergism between the antiproliferative activities of arabinosyladenine and N6-benzyladenosine.

N6-Benzyladenosine is a competitive inhibitor of adenosine deaminase from L-1210 cells in axenic culture as well as a potent antiproliferative agent in vitro and in vivo. Potentiation of the growth inhibitory activity of 9-beta-D-arabinosyladenine (ara-A) was observed in the L-1210 system with maximum synergism with a mixture of 16 micron ara-A and 10 micron benzyladenosine. Kinetic studies with L-1210 cell lysates showed values for Km of 0.25 mM ara-A and Ki of 0.23 mM benzyladenosine. It is suggested that ara-A and benzyladenosine in suitable combination may be expected to demonstrate enhanced clinical chemotherapeutic effectiveness.

Adenosine↗